The objective of the proposed research is to find a new index of ventricular contractility which is independent of end-diastolic ventricular volume and afterloaded systolic pressure yet changes markedly if the contractile state of the ventricle varies. In dog experiments, we have shown that the time-varying ratio, E(t), of instantaneous intraventricular pressure, P(t), to instantaneous intraventricular volume, V(t), serves as a good index of contractility. E(t), defined as P(t)/(V(t)-Vd), was independent of end-diastolic ventricular volume and systolic pressure when the contractile state was maintained constant, whereas it was very sensitive to changes in the inotropic state of the ventricle. Vd in the equation represents that part of the ventricular volume which does not participate in active pressure generation. In this renewal application, we propose to study whether the time- varying pressure-diameter ratio of the dog's and baboon's ventricle Ed(t) has similar characteristics as the pressure-volume ratio Ed(t). Ventricular internal diamter is to be measured by ultrasonic devices. First, we will study both Ed(t) and Ed(t) simultaneously in excised dog's hearts to analyze the correlation between the two ratios. We will then confirm in conscious dogs and baboons with denervated heart that Ed(t) is independent of the preload and afterload as was Ed(t). Finally, we plan to study Ed(t) in the baboon with intact cardiac nerves to quantitate neural and humoral control of ventricular contractility and the effect of coronary ischemia. In these experiments other indexes of ventricular contractility (e.g., dP/dt and isometric wall force) will be compared against Ed(t) to evaluate its relative utility. Thus, we hope to establish the basis for clinical application of ED(t).